反应详情

温度

-78 °C

Potassium tert-butoxide (7.92 g, 70.5 mmol) was dissolved in THF (150 mL) and cooled to −78° C. 2-Fluoro-5-methoxybenzoic acid (3.00 g, 17.6 mmol) in THF (100 mL) was added followed by n-butyl lithium (2.5 N in hexanes, 28.2 mL, 70.5 mmol). After 40 minutes, iodomethane (2.2 mL, 35.4 mmol) was added and allowed to stir at −78° C. for 70 minutes before warming to room temperature. The reaction was quenched with saturated ammonium chloride (100 mL) and extracted with ether. The aqueous layer was acidified using 6 N HCl then extracted with ether. The organic layer was dried over sodium sulfate, filtered and concentrated. The crude material was purified by Gilson reverse-phase HPLC (acidic mobile phase) to yield 2-fluoro-5-methoxy-4-methylbenzoic acid as a white solid. MS m/z=185 [M+1]+. Calc'd for C9H9FO3: 184.20.

1. temperaturebefore warming to room temperature
2. customThe reaction was quenched with saturated ammonium chloride (100 mL)
3. extractionextracted with ether
4. extractionthen extracted with ether
5. dry with materialThe organic layer was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude material was purified by Gilson reverse-phase HPLC (acidic mobile phase)